Methotrexate-induced intestinal mucositis delays gastric emptying and gastrointestinal transit of liquids in awake rats

Abstract

-Context -Methotrexate and other anticancer agents can induce intestinal mucositis, which is one of the most common limiting factor that prevent further dose escalation of the methotrexate. Objectives -To evaluate the gastric emptying and gastrointestinal transit of liquids in methotrexate-induced intestinal mucositis. Methods -Wistar rats received methotrexate (2.5 mg/kg/day for 3 days, subcutaneously) or saline. After 1, 3 and 7 days, sections of duodenum, jejunum and ileum were removed for assessment of epithelial damage and myeloperoxidase activity (biochemical marker of granulocyte infiltration). Others rats were pre-treated with methotrexate or saline, gavage-fed after 3 or 7 days with a standard test liquid meal, and sacrificed 10, 20 or 30-min later. Gastric and small intestine dye recoveries were measured by spectrophotometry. Results -After 3 days of methotrexate, there was an epithelial intestinal damage in all segments, with myeloperoxidase activity increase in both in duodenum and ileum. Seven days after methotrexate, we observed a complete reversion of this intestinal damage. There was an increase in gastric dye recoveries after 10, 20, and 30-min post-prandial intervals after 3 days, but not after 7 days, of methotrexate. Intestine dye recoveries were decreased in the first and second segments at 10 min, in the third at 20 min, and in the second and third at 30 min, only after 3 days of methotrexate treatment. Conclusion -Methotrexate-induced intestinal mucositis delays gastric emptying and gastrointestinal transit of liquids in awake rats. HEADINGS -Mucositis. Methotrexate. Gastric emptying. Gastrointestinal transit. Rats.

In a Methotrexate-Induced Model of Intestinal Mucositis, Olmesartan Reduced Inflammation and Induced Enteropathy Characterized by Severe Diarrhea, Weight Loss, and Reduced Sucrose Activity

“…Previously, MTX-induced mucositis has been characterized by inflammation and increased expression and levels of MPO. 20) In the present study, high levels of MPO activity were also detected throughout the small intestines of the MTX-treated rats. Gastrointestinal toxicity due to MTX is largely due to the high rate of proliferation that enterocytes undergo, and the subsequent cell death that is induced by this pro-oxidant compound that depletes dihydrofolate pools.…”

Effects of nimesulide on the small intestine mucositis induced by methotrexate in rats

“…It has been reported that nimesulide prevents intestinal pathology induced with acetic acid and leukotriene in rats and decreases the activity of MPO which is a proinflammatory parameter [22]. Inflammation and increased MPO expression are important markers of intestinal mucositis [23]. Nimesulide has also been found to suppress MPO and significantly prevent the reduction of GSH that were increased in intestinal tissue created with burn [20].…”

Effects of resveratrol on methotrexate-induced intestinal injury

“…Previous studies have shown that a single dose of MTX is suffi cient in the development of ileal damage (24), together with villous atrophy, fl attening of the epithelium, crypt loss and restructuring of the crypts (9,26). Damage evaluation in intestinal mucosal revealed damage the 72nd h following MTX administration (22). In this study we evaluated ileal damage histopathologically and biochemically at the end of the 3rd day after MTX administration.…”

“…MTX is one of the most frequently used anti-metabolitic agents in clinical oncology. Clinical use is frequently accompanied by diarrhea and gastrointestinal symptoms (22,23). Ileal injury developing with the administration of MTX has been identifi ed in the literature (10,23,24,25).…”